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Clinical Utility of the Percentage of Positive Prostate Biopsies in Defining Biochemical Outcome After Radical Prostatectomy for Patients With Clinically Localized Prostate Cancer

From the Joint Center for Radiation Therapy, Harvard Medical School, and Departments of Pathology and Urology, Brigham and Women’s Hospital, Boston; Department of Mathematical Sciences, Worcester Polytechnic Institute, Worcester, MA; Departments of Radiation Oncology, Urology, and Pathology, Hospital of the University of Pennsylvania, Philadelphia; and Department of Mathematics, Millersville University, Millersville, PA.

Address reprint requests to Anthony V. D’Amico, MD, PhD, Joint Center for Radiation Therapy, Harvard Medical School, 330 Brookline Ave, 5th Floor, Boston, MA 02215; email adamico{at}jcrt.harvard.edu

	ABSTRACT

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

 
PURPOSE: To determine the clinical utility of the percentage of positive prostate biopsies in predicting prostate-specific antigen (PSA) outcome after radical prostatectomy (RP) for men with PSA-detected or clinically palpable prostate cancer.

METHODS: A Cox regression multivariable analysis was used to determine whether the percentage of positive prostate biopsies provided clinically relevant information about PSA outcome after RP in 960 men while accounting for the previously established risk groups that are defined according to pretreatment PSA level, biopsy Gleason score, and the 1992 American Joint Committee on Cancer (AJCC) clinical T stage. The findings were then tested using an independent surgical database that included data for 823 men.

RESULTS: Controlling for the known prognostic factors, the percentage of positive prostate biopsies added clinically significant information (P < .0001) regarding time to PSA failure after RP. Specifically, 80% of the patients in the intermediate-risk group (1992 AJCC T2b, or biopsy Gleason 7 or PSA > 10 ng/mL and 20 ng/mL) could be classified into either an 11% or 86% 4-year PSA control cohort using the preoperative prostate biopsy data. These findings were validated in the intermediate-risk patients using an independent surgical data set.

CONCLUSION: The validated stratification of PSA outcome after RP using the percentage of positive prostate biopsies in intermediate-risk patients is clinically significant. This information can be used to identify men with newly diagnosed and clinically localized prostate cancer who are at high risk for early ( 2 years) PSA failure and, therefore, may benefit from the use of adjuvant therapy.

	INTRODUCTION

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THE PROSTATE-SPECIFIC antigen (PSA) level, biopsy Gleason score, and the 1992 American Joint Committee on Cancer (AJCC) clinical T stage have been established as comprising the first step toward defining the probability of organ-confined prostate cancer in an individual patient before the delivery of definitive treatment.¹ Yet, although finding organ-confined prostate cancer at the time of pathologic sectioning of the radical prostatectomy (RP) specimen is a favorable prognostic factor, it does not guarantee PSA control. PSA failure occurs despite pathologic evidence of organ-confined disease in some men.^2,3

PSA has been used for evaluating treatment success or failure. Whether PSA can be used as a surrogate end point for cause-specific survival after a radical retropubic prostatectomy awaits further follow-up. Nevertheless, treatment recommendations after primary treatment failure are often made on the basis of the PSA end point. The availability of PSA outcome data after RP would provide a useful tool for counseling patients about PSA outcome after RP and also for selecting patients who are unlikely to remain PSA failure–free after RP alone for inclusion in adjuvant therapy trials. The question remains, however, as to the most predictive and reproducible clinical variables on which to base the PSA outcome data.

Previously published studies^4-6 confirm that the serum PSA level, 1992 AJCC clinical T stage, and biopsy Gleason score are independent predictors of PSA failure–free survival after either RP or external-beam radiation therapy (RT). Risk groups that are defined according to PSA level, biopsy Gleason score, and the 1992 AJCC clinical T stage and that identify the risk of PSA failure after RP or RT have been previously published.⁷

The fraction of prostate biopsies that are found to contain prostate cancer represents information that is readily available for all patients with PSA-detected or clinically palpable prostate cancer. Studies investigating the ability of the fraction of positive prostate biopsies x 100 to predict pathologic end points after RP suggest a role for this clinical factor in predicting tumor volume,⁸ extracapsular extension (ECE),^9,10 seminal vesicle invasion (SVI),¹¹ lymph node involvement,¹² and the percentage of Gleason score 4 and 5 disease in the RP specimen.¹³ Yet whether the percentage of positive prostate biopsies provides information in addition to that which is already embodied in the known prognostic factors involved in predicting PSA control after RP has not been clearly elucidated.

This study had two goals. The first goal was to establish whether the percentage of positive prostate biopsies provided further clarity in predicting PSA outcome after RP after accounting for the previously published prognostic risk groups⁷ in men with PSA-detected or clinically palpable prostate cancer. The second goal was to test the results using a validation analysis that used a second independent surgical data set. Particular attention was given to the patients who were classified in the intermediate-risk group,⁷ for whom improvements in the prediction of PSA outcome are most needed.

	METHODS

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Patient Population
Nine hundred sixty men treated with an RP and bilateral pelvic lymph node dissection at the Hospital of the University of Pennsylvania (PENN; Philadelphia, PA) between 1989 and 1998 who had PSA-detected or clinically palpable prostate cancer comprised the study population. Patients who received neoadjuvant androgen-suppression therapy or adjuvant RT and/or androgen-suppression therapy were excluded. Eight hundred twenty-three men treated with an RP and bilateral pelvic lymph node dissection at the Brigham and Women’s Hospital (B&W) between 1989 and 1998 who had PSA-detected or clinically palpable prostate cancer comprised the validation cohort. Table 1 lists the preoperative clinical and postoperative pathologic characteristics for the 960 study patients and the 823-member validation cohort.

Follow-Up
The median durations of follow-up for the 960 and 823 surgically managed patients at PENN and B&W were 46 months (range, 8 to 100 months) and 52 months (range, 8 to 118 months), respectively. The patients were examined 1 month postoperatively and then at 3-month intervals for 2 years, every 6 months for 5 years, and annually thereafter. At each follow-up appointment, the serum PSA level was measured before the DRE was performed. All pretreatment PSA values were obtained within 1 month of the date of surgery. No patients were lost to follow-up.

Statistical Analyses
A Cox regression time-to-PSA-failure analysis¹⁸ that evaluated the ability of the percentage of positive biopsies to predict time to PSA failure was performed for all study patients. The assumptions of the Cox model were tested and met. The percentage of positive biopsies and the preoperative PSA level were treated as both continuous and categorical variables in separate analyses. The biopsy Gleason score was evaluated twice: first as a continuous variable that could take on integer values of 2 through 10 and second as a categorical variable that was grouped as 2 to 4, 5 to 6, 7, and 8 to 10 in the second analysis. The 1992 AJCC clinical T stage was evaluated first as a continuous and second as a categorical variable that could take on values of T1c, T2a, T2b, or T2c. Baseline groups for the categorical variables were biopsy Gleason score of 2 to 4 and 1992 AJCC stage T1c. When PSA was treated as a categorical variable, values were grouped in a standard fashion (0 to 4, > 4 to 10, > 10 to 20, and > 20 to 50 ng/mL) to allow comparison with results of other published series. The percentages of positive prostate biopsies were grouped as less than 34%, 34% to 50%, and greater than 50%. Baseline groups for PSA and the percentage of positive prostate biopsies were 0 to 4 ng/mL and less than 34%, respectively. Patients with 1992 AJCC clinical stage T1a or T1b disease were excluded because the diagnosis of prostate cancer in these cases was made on the basis of a transurethral resection sample of the prostate and not through the use of multiple needle-biopsy specimens. Race was not included in the multivariable analysis because most patients were of the same race; therefore, the power to detect any difference according to race was low.

PSA failure was considered to have occurred when two consecutive detectable PSA values were obtained after an undetectable value. Time zero was defined as the date of surgery for all patients. If a PSA never became undetectable postoperatively, then PSA failure was considered to have occurred at time equal to zero. Patients who were found to have positive pelvic lymph nodes at the time of frozen section or at final pathologic section were started on androgen-suppression therapy and, therefore, were considered to have experienced treatment failure at time zero. The probability of 2-year PSA failure was calculated from the coefficients of the Cox model. The 95% confidence intervals for the 2-year PSA-failure probabilities were calculated using a bootstrapping procedure¹⁹ with 2,000 replications. The marginal proportion of variation explained (mPVE)²⁰ for each of the significant clinical predictors of time to PSA failure were also calculated. The mPVE value defines the percentage of the variation in the PSA data that can be explained by the predictor and can range from 0% to 100%. The test for linear trend between pretreatment clinical predictors and pathologic outcomes was performed using a Cochran-Armitage test.²¹

Three risk groups previously defined⁷ from a review of the literature^22-33 that are based on the pretreatment PSA level, biopsy Gleason score, and 1992 AJCC T stage were used to illustrate the impact that the percentage of positive biopsy information had on the PSA failure–free (bNED) survival rates after RP. Low-risk patients had a preoperative PSA level of 10 ng/mL, a biopsy Gleason score of 6, or 1992 AJCC clinical stage T1c or T2a disease. Intermediate-risk patients had a PSA level of greater than10 but 20 ng/mL, a biopsy Gleason score of 7, or 1992 AJCC clinical stage T2b disease. Finally, high-risk patients had a PSA level of greater than 20 ng/mL, a biopsy Gleason score of 8, or 1992 AJCC clinical stage T2c disease. Specifically, PSA failure–free survival (stratified by < 34%, 34% to 50%, and > 50% positive biopsies) was estimated using the actuarial method of Kaplan and Meier³⁴ and graphically displayed. The cutoff points for the percentage of positive biopsy variables were selected to evaluate the clinical utility of this parameter and were defined before the statistical analysis was performed.

A validation analysis of the ability of the percentage of positive biopsies to stratify PSA outcome after RP was performed using an independent surgical database that included data for 823 men with clinically localized prostate cancer who were managed at a separate institution during the same time period as the study cohort.

	RESULTS

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Pretreatment Clinical Characteristics and Pathologic Stage
The clinical characteristics and corresponding pathologic stages are listed in Table 1 for the 960 study patients. There was a statistically significant decrease in the pathologic organ-confinement rate, with an increasing value of the PSA (P < .0001), 1992 AJCC clinical stage (P < .0001), biopsy Gleason score (P < .0001), and the percentage of positive biopsies (P < .0001). Conversely, the finding of established ECE or SVI increased significantly as the preoperative PSA value (ECE, P < .0001; SVI, P < .0001), 1992 AJCC clinical stage (ECE, P < .0001; SVI, P < .0001), biopsy Gleason score (ECE, P < .0001; SVI, P < .0001), or percentage of positive biopsies (ECE, P < .0001; SVI, P < .0001) increased. No significant trend (P .38) was noted for the pathologic finding of focal ECE as a function of the pretreatment PSA level, biopsy Gleason score, 1992 AJCC clinical stage, or percentage of positive biopsies.

Time-to-PSA-Failure Analysis
As continuous variables, the pretreatment PSA level (P < .0001), biopsy Gleason score (P = .0003), 1992 AJCC clinical T stage (P = .05), and percentage of positive biopsies (P < .0001) were all independent significant predictors of time to PSA failure. PSA and the percentage of positive biopsies remained significant (P < .0001) when the biopsy Gleason score and 1992 AJCC clinical T stage were evaluated as categorical variables. Table 3 lists all of the individual P values for the two Cox regression analyses in which the biopsy Gleason score and 1992 AJCC T stage were evaluated first as continuous and then as categorical variables.

View larger version (20K): [in this window] [in a new window]   Fig 1. PSA failure-free survival stratified by the risk group defined using the PSA value, biopsy Gleason score, and 1992 AJCC clinical T stage for study patients managed using a radical retropubic prostatectomy. Pair-wise P values: low versus intermediate risk, P < .0001; intermediate versus high risk, P < .0001; low versus high risk, P < .0001.

View larger version (17K): [in this window] [in a new window]   Fig 2. PSA failure-free survival stratified by the percentage of positive biopsies for low-risk study patients managed using a radical retropubic prostatectomy. Pair-wise P values: less than 34% versus more than 34% to 50%, P = .05; more than 34% to 50% versus more than 50%, P = .09; less than 34% versus more than 50%, P < .0001.

View larger version (18K): [in this window] [in a new window]   Fig 3. PSA failure-free survival stratified by the percentage of positive biopsies for intermediate-risk study patients managed using a radical retropubic prostatectomy. Pair-wise P values: less than 34% versus more than 34% to 50%, P = .001; more than 34% to 50% versus more than 50%, P = .03; less than 34% versus more than 50%, P < .0001.

View larger version (20K): [in this window] [in a new window]   Fig 4. PSA failure-free survival stratified by the percentage of positive biopsies for high-risk study patients managed using a radical retropubic prostatectomy. Pair-wise P values: less than 34% versus more than 34% to 50%, P = .001; more than 34% to 50% versus more than 50%, P = .03; less than 34% versus more than 50%, P < .0001.

View larger version (20K): [in this window] [in a new window]   Fig 5. PSA failure-free survival stratified by the risk group defined using the PSA value, biopsy Gleason score, and 1992 AJCC clinical T stage for validation patients managed using a radical retropubic prostatectomy. Pair-wise P values: low versus intermediate risk, P < .0001; intermediate versus high risk, P < .0001; low versus high risk, P < .0001.

View larger version (19K): [in this window] [in a new window]   Fig 6. PSA failure-free survival stratified by the percentage of positive biopsies for intermediate-risk validation patients managed using a radical retropubic prostatectomy. Pair-wise P values: less than 34% versus more than 34% to 50%, P < .0001; more than 34% to 50% versus more than 50%, P = .0001; less than 34% versus more than 50%, P < .0001.

	DISCUSSION

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

Prostate biopsy information is available for all patients with newly diagnosed prostate cancer, with the exception of the decreasing number of patients who are diagnosed today during a transurethral resection. Therefore, investigators have attempted to establish whether the number of biopsies that contain adenocarcinoma provides further information about PSA outcome after RP. In particular, Presti et al⁴² performed a Cox regression multivariate analysis to evaluate the clinical utility of the fraction of systematic biopsies (one to three v four to six), pretreatment PSA level ( 20 ng/mL v > 20 ng/mL), and biopsy Gleason score (2 to 6 v 7 to 10) in predicting time to postoperative PSA failure. Their analysis included 109 patients and used two consecutive increases in PSA of more than 0.1 ng/mL as the definition of PSA failure. They found that both the biopsy Gleason score and the fraction of systematic biopsies were predictive of PSA outcome after RP.

To provide clinical utility in this study, a specific categorization of the data for percentage of positive biopsies was selected for evaluation before analysis, which corresponded to one to two (< 34%), three (34% to 50%), or four to six (> 50%) positive biopsies in the case of a standard sextant sampling. This selection was based on the presumption that more than one half of the cores being positive versus one third or fewer was a clinically meaningful difference. The percentage of positive biopsies, when analyzed in this manner, was found to be an independent predictor of time to PSA failure after RP after controlling for the previously defined risk stratification schema that was based on the known prognostic factors.⁷ The stratification of PSA outcome after RP provided by the percentage of positive biopsies was also clinically significant in that the vast majority (78% to 80%) of the intermediate-risk patients in the study and validation cohorts could be categorized into a high- or low-risk category for PSA outcome after RP. This result should translate into a marked improvement in the physician’s ability to counsel the patient regarding outcome after RP. Specifically, Table 4 lists the probability of PSA failure at 2 years and 95% confidence intervals stratified according to known prognostic factors and the categories of the percentage of positive biopsies that were selected for evaluation in this study. This information identifies patients who are at high risk for early PSA failure. Considering the recent data showing that a time to PSA failure of less than 2 years predicts for distant failure,⁴³ patients who are at high risk for early PSA failure may be the ideal candidates to select for entry onto adjuvant therapy trials.

Several issues remain that need to be addressed. First, as in this study, some patients will have prostate biopsies obtained in practice that are not sextant. The results of this study depended on an accurate sampling of the prostate gland. That all patients in this study had at least four cores obtained may be relevant to the accomplishment of this end point. Therefore, these data may not be applicable in the case of patients for whom fewer than four cores were obtained. Next, 26% of the patients in this study from the PENN cohort had seven or more biopsies obtained. Specifically, 21%, 28%, and 44% of patients with a prostate gland volume of less than 30 cm³, 30 to 75 cm³, or more than 75 cm³, respectively, had at least seven cores obtained, as listed in Table 2. This trend suggested that a larger sample was generally performed in patients with larger prostate gland volumes, possibly in an effort to decrease sampling error.⁴⁴ Therefore, the results of this study may not be applicable to patients with large gland volumes (> 75 cm³) who had fewer than seven cores obtained.

Another limitation of the study is that the results are based on PSA control and not patterns of failure or cause-specific survival data. However, a recent study⁴⁵ has suggested that PSA failure may be a surrogate end point for death from prostate cancer for patients undergoing a radical perineal prostatectomy. Validation of this finding by others and for patients undergoing a radical retropubic prostatectomy is needed to establish PSA failure as a surrogate end point for death from prostate cancer.

Finally, the percentages of positive prostate biopsies of less than 34%, 34% to 50%, and more than 50% corresponded to positive surgical margin rates of 13%, 28%, and 35%, respectively, for the study cohort and 11%, 29%, and 37%, respectively, for the validation cohort. Therefore, it is conceivable that the use of adjuvant RT may benefit men with more than 50% positive prostate biopsies. A future study will address whether the factor of percentage of positive prostate biopsies retains its prognostic significance in a group of patients undergoing RP followed by adjuvant RT.

In conclusion, the percentage of positive prostate biopsies represents information that is routinely available for patients with newly diagnosed prostate cancer. This information has now been shown to provide a clinically significant improvement in predicting PSA outcome after RP for patients for whom it is most needed. Therefore, this information may be used to select men with clinically localized prostate cancer who are at very high risk of early PSA failure ( 2 years) for inclusion in adjuvant therapy trials.

	REFERENCES

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

 
1. Partin AW, Kattan MW, Subong ENP, et al: Combination of prostate specific antigen, clinical stage, and Gleason score to predict pathologic stage of localized prostate cancer: A multi-institutional update. JAMA 277:1445-1452, 1997[Abstract/Free Full Text]

2. D’Amico AV, Whittington R, Malkowicz SB, et al: Prostate-specific antigen failure despite pathologically organ-confined and margin-negative prostate cancer: The basis for an adjuvant therapy trial. J Clin Oncol 15:1465-1469, 1997[Abstract]

3. Lerner SE, Blute ML, Bergstralh EJ, et al: Analysis of risk factors for progression in patients with pathologically organ confined prostate cancers after radical retropubic prostatectomy. J Urol 156:137-143, 1996[Medline]

4. Kupelian P, Katcher J, Levin HS, et al: Stage T1–2 prostate cancer: A multivariate analysis of factors affecting biochemical and clinical failures after radical prostatectomy. Int J Radiat Oncol Biol Phys 37:1043-1052, 1997[Medline]

5. D’Amico AV, Whittington R, Kaplan I, et al: Equivalent biochemical failure free survival after external beam radiation therapy or radical prostatectomy in patients with a pretreatment prostate specific antigen of > 4-20 ng/ml. Int J Radiat Oncol Biol Phys 37:1053-1058, 1997[Medline]

6. Kattan MW, Easthan JA, Stapleton AMF, et al: A preoperative nomogram for disease recurrence following radical prostatectomy for prostate cancer. J Natl Cancer Inst 90:766-771, 1998[Abstract/Free Full Text]

7. D’Amico AV, Whittington R, Broderick GA, et al: Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA 280:969-974, 1998[Abstract/Free Full Text]

8. Terris MK, Haney DJ, Johnstone IM, et al: Prediction of prostate cancer volume using prostate-specific antigen levels, transrectal ultrasound, and systematic sextant biopsies. Urology 45:75-80, 1995[Medline]

9. Borirakchanyavat S, Bhargava V, Shinohara K, et al: Systematic sextant biopsies in the prediction of extracapsular extension at radical prostatectomy. Urology 50:373-378, 1997[Medline]

10. Badalment RA, Miller MC, Peller PA, et al: An algorithm for predicting non-organ confined prostate cancer using the results obtained from sextant core biopsies with prostate specific antigen level. J Urol 156:1375-1380, 1996[Medline]

11. D’Amico AV, Whittington R, Malkowicz SB, et al: Role of percent positive biopsies and endorectal coil MRI in predicting prognosis in intermediate-risk prostate cancer patients. Cancer J Sci Am 2:343-350, 1996[Medline]

12. Conrad S, Graefen M, Pichlmeier ,et al: Systematic sextant biopsies improve preoperative prediction of pelvic lymph node metastases in patients with clinically localized prostate carcinoma. J Urol 159:2023-2029, 1998[Medline]

13. Epstein JI, Walsh PC, Carmichael M, et al: Pathologic and clinical findings to predict tumor extent of nonpalpable (stage T1c) prostate cancer. JAMA 271:368-374, 1994[Abstract/Free Full Text]

14. Gleason DF: Histologic grading and staging of prostatic carcinoma, in Tannenbaum M (ed): Urologic Pathology. Philadelphia, PA,Lea & Febiger, 1977, pp 171-187

15. Beahrs OH, Henson DE, Hutter RVP: American Joint Committee on Cancer Manual for Staging Cancer (ed 4). Philadelphia, PA,JB Lippincott, 1992

16. Oesterling JE, Jacobsen SJ, Klee GG, et al: Free, complexed and total serum prostate specific antigen: The establishment of appropriate reference ranges for their concentrations and ratios. J Urol 154:1090-1095, 1995[Medline]

17. Epstein JI, Pizov G, Walsh PC: Correlation of pathologic findings with progression after radical retropubic prostatectomy. Cancer 71:3582-3589, 1993[Medline]

18. Neter J: Simultaneous inferences and other topics in regression analysis-1, in Neter J, Wasserman W, Kutner M (eds): Applied Linear Regression Models (ed 1). Homewood, IL,Richard D. Irwin, Inc, 1983, pp 150-153

19. Efron R, Tibsherani R: An Introduction to the Bootstrap. New York, NY,Chapman and Hall, 1993

20. Schemper M: The relative importance of prognostic factors in studies of survival. Stat Med 12:2377-2402, 1993[Medline]

21. Armitage P: Test for linear trend in proportions and frequencies. Biometrics 11:375-384, 1955

22. Zagars GK, Pollack A, Kavadi VS, et al: Prostate specific antigen and radiation therapy for clinically localized prostate cancer. Int J Radiat Oncol Biol Phys 32:293-306, 1995[Medline]

23. Pisansky TM, Kahn MJ, Rasp GM, et al: A multiple prognostic index predictive of disease outcome after irradiation for clinically localized prostate cancer. Cancer 79:337-344, 1997[Medline]

24. Lee WR, Hanks GE, Schultheiss TE, et al: Localized prostate cancer treated by external beam radiotherapy alone: Serum prostate-specific antigen–driven outcome analysis. J Clin Oncol 13:464-469, 1995[Abstract/Free Full Text]

25. Pisansky TM, Cha SS, Earle JD, et al: Prostate-specific antigen as a pretherapy prognostic factor in patients treated with radiation therapy for clinically localized prostate cancer. J Clin Oncol 11:2158-2166, 1993[Abstract/Free Full Text]

26. Zietman AL, Coen JJ, Shipley WU, et al: Radical radiation therapy in the management of prostatic adenocarcinoma: The initial prostate specific antigen value as a predictor of treatment outcome. J Urol 151:640-645, 1994[Medline]

27. Hanks GE, Lee WR, Schultheiss TE: Clinical and biochemical evidence of control of prostate cancer at 5 years after external beam radiation. J Urol 154:456-459, 1995[Medline]

28. Partin AW, Piantadosi S, Sanda MG, et al: Selection of men at high risk for disease recurrence for experimental adjuvant therapy following radical prostatectomy. Urology 45:831-838, 1995[Medline]

29. Zietman AL, Edelstein RA, Coen JJ, et al: Radical prostatectomy for adenocarcinoma of the prostate: The influence of preoperative and pathologic findings on biochemical disease-free outcome. Urology 43:828-833, 1994[Medline]

30. D’Amico AV, Whittington R, Malkowicz SB, et al: Outcome based staging for clinically localized adenocarcinoma of the prostate. Urol 158:1422-1426, 1997

31. Ragde H, Blasko JC, Grimm PD, et al: Interstitial iodine-125 radiation without adjuvant therapy in the treatment of clinically localized prostate carcinoma. Cancer 80:442-453, 1997[Medline]

32. Blasko JC, Wallner K, Grimm PD, et al: Prostate specific antigen based disease control following ultrasound guided I 125 implantation for stage T1/T2 prostatic carcinoma. J Urol 154:1096-1099, 1995[Medline]

33. Wallner K, Roy J, Harrison L: Tumor control and morbidity following transperineal iodine 125 implantation for stage T1/T2 prostatic carcinoma. J Clin Oncol 14:449-453, 1996[Abstract/Free Full Text]

34. Kaplan EL, Meier P: Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457-481, 1958

35. Ismail MT, Petersen RO, Alexander AA, et al: Tumor vascularity assessed by color Doppler imaging in prostate cancer: Prognostic implications. J Urol 159:288, 1998 (abstr 1110)

36. D’Amico AV, Whittington R, Tomaszewski JE, et al: Critical analysis of the ability of the endorectal coil magnetic resonance imaging scan to predict pathologic stage, margin status, and postoperative prostate-specific antigen failure in patients with clinically organ-confined prostate cancer. J Clin Oncol 14:1770-1777, 1996[Abstract/Free Full Text]

37. Yang RM, Naitoh J, Murphy M, et al: Low P27 Expression predicts poor disease-free survival in patients with prostate cancer. J Urol 159:941-945, 1998[Medline]

38. Stapleton AM, Zbell P, Kattan MW, et al: Assessment of the biologic markers p53, Ki-67, and apoptotic index as predictive indicators of prostate carcinoma recurrence after surgery. Cancer 82:168-174, 1998[Medline]

39. Waltregny D, de Leval L, Menard S, et al: Independent prognostic value of the 67-kd laminin receptor in human prostate cancer. Natl Cancer Inst 89:1224-1228, 1997[Free Full Text]

40. Theodorescu D, Broder SR, Boyd JC, et al: Cathepsin D and chromogranin A as predictors of long term disease specific survival after radical prostatectomy for localized carcinoma of the prostate. Cancer 80:2109-2112, 1997[Medline]

41. Snow PB, Levine RF, Ziada AM, et al: Impact of different variables on outcome of treatments for clinically confined prostate cancer: Prediction of response and pathological stage of the disease using a neural network. J Urol 159:295, 1998 (abstr 1136)

42. Presti JC Jr, Shinohara K, Bacchetti P, et al: Positive fraction of systematic biopsies predicts risk of relapse after radical prostatectomy. Urology 52:1079-1084, 1998[Medline]

43. Vashi AR, Wojno KJ, Gillespie B, et al: A model for the number of core per prostate biopsy based on patient age and prostate gland volume. J Urol 159:920-924, 1998[Medline]

44. Pound CR, Partin AW, Eisenberger MA, et al: Natural history of progression after PSA elevation following radical prostatectomy. JAMA 281:1591-1597, 1999[Abstract/Free Full Text]

45. Iselin CE, Robertson JE, Paulson DF: Radical perineal prostatectomy: Oncological outcome during a 20-year period. J Urol 161:163-168, 1999[Medline]

Submitted June 17, 1999; accepted November 4, 1999.

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				A. V. D'Amico, J. Moul, P. R. Carroll, L. Sun, D. Lubeck, and M.-H. Chen Cancer-Specific Mortality After Surgery or Radiation for Patients With Clinically Localized Prostate Cancer Managed During the Prostate-Specific Antigen Era J. Clin. Oncol., June 1, 2003; 21(11): 2163 - 2172. [Abstract] [Full Text] [PDF]

				Y. Matsui, S. Egawa, C. Tsukayama, A. Terai, S. Kuwao, S. Baba, and Y. Arai Artificial Neural Network Analysis for Predicting Pathological Stage of Clinically Localized Prostate Cancer in the Japanese Population Jpn. J. Clin. Oncol., December 1, 2002; 32(12): 530 - 535. [Abstract] [Full Text] [PDF]

				A. V. D'Amico Predicting Prostate-Specific Antigen Recurrence Established: Now, Who Will Survive? J. Clin. Oncol., August 1, 2002; 20(15): 3188 - 3190. [Full Text] [PDF]

				M. Graefen, P. I. Karakiewicz, I. Cagiannos, D. I. Quinn, S. M. Henshall, J. J. Grygiel, R. L. Sutherland, P. D. Stricker, E. Klein, P. Kupelian, et al. International Validation of a Preoperative Nomogram for Prostate Cancer Recurrence After Radical Prostatectomy J. Clin. Oncol., August 1, 2002; 20(15): 3206 - 3212. [Abstract] [Full Text] [PDF]

				F. Cornud, T. Flam, L. Chauveinc, K. Hamida, Y. Chretien, A. Vieillefond, O. Helenon, and J. F. Moreau Extraprostatic Spread of Clinically Localized Prostate Cancer: Factors Predictive of pT3 Tumor and of Positive Endorectal MR Imaging Examination Results Radiology, July 1, 2002; 224(1): 203 - 210. [Abstract] [Full Text]

				C. K. Cross, D. Shultz, S. B. Malkowicz, W. C. Huang, R. Whittington, J. E. Tomaszewski, A. A. Renshaw, J. P. Richie, and A. V. D'Amico Impact of Race on Prostate-Specific Antigen Outcome After Radical Prostatectomy for Clinically Localized Adenocarcinoma of the Prostate J. Clin. Oncol., June 15, 2002; 20(12): 2863 - 2868. [Abstract] [Full Text] [PDF]

				P. R. Carroll Prostate Biopsy: A Wealth of Information When Done and Interpreted Correctly J. Clin. Oncol., March 13, 2000; 18(6): 1161 - 1163. [Full Text] [PDF]

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